Fetal alcohol spectrum disorders (FASDs) arise from the teratogenic effects of alcohol exposure, in utero, and are an important public health concern as they encompass one of the largest preventable causes of developmental disability. Specifically, deficits in cognitive function are the major contributor to long-lasting morbidity associated with these disorders, and are thought to relate to the broad spectrum of structural brain abnormalities that have also been observed in individuals with FASDs. Executive functioning is one cognitive domain that is particularly affected by fetal alcohol exposure, and includes an important set of cognitive control mechanisms that normally continue to develop through adolescence and help to modulate many other lower order cognitive and motor functions. These actions are thought to be meditated by activity in the frontal lobe, and functional deficits in these areas in children with FASDs may be related to abnormalities in white matter development that have also been observed in the context of fetal alcohol exposure. While frontal lobe white matter maturation also shows a protracted developmental trajectory, and has been related to advancements in executive functioning in typical development, a possible relationship between executive function deficits and white matter abnormalities in FASDs has not been investigated. This proposal aims to apply emerging diffusion magnetic resonance imaging (MRI) techniques, which allow for greater localization and an enhanced focus on developmental timing, to map white matter structural development and its relationship to executive functioning advancements in a sample of typically developing controls. These normative data will then be used as a benchmark for an investigation into the effects of prenatal alcohol exposure on executive function, white matter development, and their relationship. Most importantly, the results of these brain mapping efforts will be integrated into a broader classification framework to determine if indices of white matter development can help predict the level of executive function deficit among individuals with FASDs. This work may eventually lead to a better characterization of the precise functional deficits that affect each patient, and facilitate the application of the most appropriate clinical interventions for each individual at an earlier time point than what is allowed by neuropsychological testing alone.

Public Health Relevance

Fetal alcohol exposure is one of the largest preventable sources of developmental disability. By mapping white matter maturation and its relationship to executive functioning advances in both typical development and fetal alcohol spectrum disorders (FASDs), we may be able to develop useful predictive models that can aid in the application of personalized clinical interventions tailored to the specific functional deficits of each individual child.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30AA020431-03
Application #
8461708
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Matochik, John A
Project Start
2011-05-01
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
3
Fiscal Year
2013
Total Cost
$47,232
Indirect Cost
Name
University of California Los Angeles
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Lebel, Catherine; Warner, Tamara; Colby, John et al. (2013) White matter microstructure abnormalities and executive function in adolescents with prenatal cocaine exposure. Psychiatry Res 213:161-8
Colby, John B; Soderberg, Lindsay; Lebel, Catherine et al. (2012) Along-tract statistics allow for enhanced tractography analysis. Neuroimage 59:3227-42